A5015478157- Muscle Physiology and Disorders
- Estrogen and related hormone effects
- Genetic Neurodegenerative Diseases
- RNA Research and Splicing
- Tissue Engineering and Regenerative Medicine
- Peptidase Inhibition and Analysis
- Autophagy in Disease and Therapy
- Cancer therapeutics and mechanisms
- Mesenchymal stem cell research
- Neurogenetic and Muscular Disorders Research
- Cardiomyopathy and Myosin Studies
- Nuclear Structure and Function
- Genetics and Neurodevelopmental Disorders
- DNA Repair Mechanisms
- Adipose Tissue and Metabolism
- Virus-based gene therapy research
- RNA modifications and cancer
- Mitochondrial Function and Pathology
- Cellular transport and secretion
- Pluripotent Stem Cells Research
- CRISPR and Genetic Engineering
- HER2/EGFR in Cancer Research
- Biochemical and Molecular Research
- RNA Interference and Gene Delivery
- Silk-based biomaterials and applications
Universidade do Porto
2024
Nationwide Children's Hospital
2021-2023
Universidade de São Paulo
2011-2021
Sorbonne Université
2021
Institut de Myologie
2021
Centre de Recherche en Myologie
2021
Inserm
2021
Universidade Estadual Paulista (Unesp)
2020
Universidade Federal de Minas Gerais
2020
AstraZeneca (United Kingdom)
2012-2016
Abstract Fulvestrant is an estrogen receptor (ER) antagonist administered to breast cancer patients by monthly intramuscular injection. Given its present limitations of dosing and route administration, a more flexible orally available compound has been sought pursue the potential benefits this drug in with advanced metastatic disease. Here we report identification characterization AZD9496, nonsteroidal small-molecule inhibitor ERα, which potent selective downregulator ERα vitro vivo...
The discovery of an orally bioavailable selective estrogen receptor downregulator (SERD) with equivalent potency and preclinical pharmacology to the intramuscular SERD fulvestrant is described. A directed screen identified 1-aryl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole motif as a novel, druglike ER ligand. Aided by crystal structures novel ligands bound construct, medicinal chemistry iterations led...
Abstract Satellite cells (SCs) are the main muscle stem responsible for its regenerative capacity. In muscular dystrophies, however, a failure of process results in degeneration and weakness. To analyze effect different degrees SCs behavior, we studied adult dystrophic strains: DMD mdx , Large myd / with variable histopathological alterations. Similar were observed models, which maintained normal levels PAX7 expression, retained Pax7-positive pool, their proliferation Moreover, elevated...
Summary Methylglyoxal ( MG ) elicits activation of K + efflux systems to protect cells against the toxicity electrophile. ChIP ‐chip targeting RNA polymerase, supported by a range other biochemical measurements and mutant creation, was used identify genes transcribed in response which complement this rapid response. The SOS DNA repair regulon is induced at cytotoxic levels , even when exposure transient. Glyoxalase I alone among core protective exposure. Increased expression an indirect...
Limb girdle muscular dystrophy type 2G (LGMD2G) is a subtype of autosomal recessive caused by mutations in the telethonin gene. There are few LGMD2G patients worldwide reported, and this first description associated with early tibialis anterior sparing on muscle image myopathic-neurogenic motor unit potentials.Here we report 31 years old caucasian male patient progressive gait disturbance, severe lower limb proximal weakness since age 20 years, subtle facial weakness. Computed tomography...
Quantitative nuclear magnetic resonance imaging (MRI) has been considered a promising non-invasive tool for monitoring therapeutic essays in small size mouse models of muscular dystrophies. Here, we combined MRI (anatomical images and transverse relaxation time constant—T2—measurements) to texture analyses the study four strains covering wide range dystrophic phenotypes. Two still unexplored dystrophies were analyzed: The severely affected Largemyd recently generated worst double mutant...
The mdx mouse is a good genetic and molecular murine model for Duchenne Muscular Dystrophy (DMD), progressive devastating muscle disease. However, this inappropriate testing new therapies due to its mild phenotype. Here, we transferred the mutation 129/Sv strain with aim create more severe DMD. Unexpectedly, functional analysis of first three generations mdx129 showed amelioration phenotype, associated less connective tissue replacement, regeneration than original mdxC57BL. Transcriptome...
X-linked myopathy with excessive autophagy (XMEA) is a genetic disease associated weakness of the proximal muscles. It caused by mutations in VMA21 gene, coding for chaperone that functions vacuolar ATPase (v-ATPase) assembly. Mutations lower content assembled v-ATPases lead to an increase lysosomal pH, culminating partial blockage macroautophagy, accumulation vacuoles undigested content. Here, we studied 5-year-old boy affected XMEA, small indel gene. Detection sarcoplasmic Lc3 (also known...
To analyze the modulation of phenotype in manifesting carriers recessive X-linked myotubular myopathy (XLMTM), searching for possible genetic modifiers.Twelve Brazilian families with XLMTM were molecularly and clinically evaluated. In 2 families, 4 6 5 female identified. These females studied X chromosome inactivation. addition, whole-exome sequencing was performed, looking modifier variants. We also determined penetrance rate among mutations responsible condition.Mutations MTM1 gene...
Dynamin 2 (DNM2) is a ubiquitously expressed protein involved in many functions related to trafficking and remodeling of membranes cytoskeleton dynamics.Mutations the DNM2 gene cause autosomal dominant centronuclear myopathy (AD-CNM), characterized mainly by muscle weakness central nuclei.Several defects have been identified KI-Dnm2 R465W/+ mouse model disease explain phenotype, including reduction satellite cells pool muscle, but functional consequences this depletion not until...
Myotonic dystrophy type 1 (DM1) is the most common form of muscular in adults and affects mainly skeletal muscle, heart, brain. DM1 caused by a CTG repeat expansion 3′UTR region DMPK gene that sequesters muscleblind-like proteins, blocking their splicing activity forming nuclear RNA foci . Consequently, many genes have reversed to fetal pattern. There no treatment for DM1, but several approaches been explored, including antisense oligonucleotides (ASOs) aiming knock down expression or bind...
We report in this work the antibacterial evaluation of 12 lipophilic fluoroquinolone derivatives containing diaminoalkyl side chains at C-7 position. The compounds were investigated against 15 bacterial strains including gram-negative and gram-positive species clinical microbiological importance. Three (5, 10 11) as active or more efficient than gatifloxacin bacteria M. lentus. When compared with compound was 16 times active. Two (11 12) twice reference S. aureus.